JULY 18, 2012
A new study shows that prostate cancer surgery, which often leaves men impotent or incontinent, does not appear to save the lives of men with early-stage disease, who account for most cases, and many of these men would do just as well to choose no treatment at all.
The findings were based on the largest-ever clinical trial comparing surgical removal of the prostate with a strategy known as "watchful waiting." They add to growing concerns that prostate cancer detection and treatment efforts over the past 25 years, particularly in the United States, have been woefully misguided, rendering millions of men impotent, incontinent and saddled with fear about a disease that was unlikely ever to kill them in the first place. About 100,000 to 120,000 radical prostatectomy surgeries are performed in the United States each year.
"I think this is game-changing," said Dr. Leonard Marks, a professor of urology at the University of California, Los Angeles, who was not involved in the study. "What this study does is call attention to the fact that there are a lot of prostate cancers that are diagnosed today that are not dangerous."
Even so, the research, published Wednesday in The New England Journal of Medicine and paid for by the Department of Veterans Affairs, the National Cancer Institute and the Agency for Healthcare Research and Quality, is unlikely to settle the debate about the best course of care for men with prostate cancer.
An editorial accompanying the report argued that the study of 731 men, while important, is still too small to draw definitive conclusions about the relative benefits of radical prostatectomy. In addition, slightly more men who did not undergo surgery developed bone metastases over the course of the 15-year study. There was no statistical difference in risk of death from prostate cancer or any cause among men who were randomly assigned to surgery or to an observation group. There was also a suggestion that men with very high scores on a prostate cancer screening test were more likely to benefit from surgery.
The study included only men with early-stage disease, about half of whom learned of their cancer as a result of the prostate specific antigen, or P.S.A., screening blood test. About 81 percent of men with prostate cancer have early-stage or localized cancer, which means it has not spread beyond the prostate. But the findings are not relevant to men with more advanced disease, who may benefit from aggressive treatment, said Dr. Ian Thompson, director of the cancer therapy and research center at the University of Texas Health Science Center in San Antonio.
"The real point is that we shouldn't focus on finding every prostate cancer because, as this study and all the screening studies show, the majority that you find don't need to be found,'' said Dr. Thompson, an author of the editorial. "What we should focus our screening on and our testing on are patients who are likely to have more aggressive tumors in which treatment seems to make a difference."
This year, about 242,000 men will receive a diagnosis of prostate cancer, largely because of screening for high levels of P.S.A. in the blood. About 28,000 men die of prostate cancer each year, making it the second-biggest cancer killer of men, second only to lung cancer. Even so, large studies now show that early detection by P.S.A. screening makes little, if any, difference in whether a man dies from prostate cancer.
In May, the United States Preventive Services Task Force issued a controversial recommendation against regular P.S.A. screening. The task force concluded that the test offers little, if any benefit, yet subjects men to anxiety and painful biopsies and often puts them on the course of invasive and risky treatment. But several medical groups have criticized the finding, and P.S.A. testing remains an entrenched part of men's health care at middle age.
The latest research, called the Prostate Cancer Intervention Versus Observation Trial, or Pivot, focuses on what happens after a man receives a diagnosis of early-stage cancer, often as a result of a P.S.A. test. The men in the study were randomly assigned either to surgical removal of the prostate or to an observation group, where a man's cancer was monitored but not treated unless it showed signs of progressing. Although the study originally set out to recruit 2,000 men, the researchers could not reach that goal and revised the research plan to include 731 men.
By the end of the 15-year study, 354 men had died, but most of them had died of from a cause other than prostate cancer. There was no statistical difference in overall mortality rates in the surgical group, which had 171 deaths, compared with the observation group, which had 183 deaths.
During the study, only 52 men, or about 7 percent of the study subjects, died of prostate cancer, but again there was no statistical difference in the prostate cancer mortality rate between the groups.
But in a secondary analysis, the researchers did find an important difference between the groups, suggesting that surgery may benefit men with early-stage disease who have a high P.S.A. score. Among men with a P.S.A. value higher than 10 nanograms per milliliter of blood, surgery lowered a man's risk of dying by 33 percent compared with the observation group. Overall, among men with high P.S.A. scores, there were 13 percent fewer deaths in the surgery group compared with the observation group. No difference was seen among men with a P.S.A. value of 10 or less.
Dr. Timothy J. Wilt, the study's lead author and professor of medicine at Minneapolis Veterans Affairs Center for Chronic Disease Outcomes Research, said he hoped the results would give patients with early-stage disease more confidence to choose watchful waiting as an option.
About 90 percent of men with early-stage disease choose immediate treatment with surgery or radiation, he said.
"Many men, when they hear about a diagnosis of prostate cancer, become fearful," Dr. Wilt said. "They think if they aren't treated they will die from it. Our results clearly demonstrate that's not true. The overwhelming majority will not die of their disease if it's left untreated."